A diversified group of scientists looking to gain a better understanding of the structure and function of lipids has been awarded a $35 million government grant from the National Institutes of Health.
After the five-year life of that grant, participating researchers hope to have made notable strides in an emerging field called "metabolomics," or the study of metabolites. Lipids are a water-insoluble subset of metabolites.
"What we now know is that even though you [identify] all the genes in a cell that doesn't tell you everything, and the genes don't necessarily correlate with the proteins, and the proteins don't necessarily correlate with the metabolites," Edward Dennis, principal investigator and professor of chemistry and biochemistry at the University of California at San Diego, told BioWorld Today. "The important question is what metabolites are in a cell. That's the concept that started us on this project."
Actually, the project is the brainchild of Dennis, who invited peers to participate from Duke University Medical School in Durham, N.C.; Georgia Institute of Technology in Atlanta; University of California at Irvine; University of Colorado School of Medicine in Denver; University of Texas Southwestern Medical School in Dallas; Vanderbilt University Medical School in Nashville, Tenn.; and Avanti Polar Lipids Inc., of Alabaster, Ala.
Both Dennis and Walt Shaw, president and CEO of Avanti, compare the study of metabolites to the genome revolution.
"I like to say that genomics was of the last century. The genomics revolution was the human genome, and we solved it," Dennis said. "The current revolution is proteomics, which is determining all the proteins in a cell. But what one really wants to know about is all the metabolites in a cell - that's the next revolution."
Shaw added, "When the genome project started, we didn't know anything about the genome, and now we do. Right now we know a little about the lipid makeup of cells, but if you could define the lipid makeup of cells and how they change with stimulation, you could begin to understand their role in the cell."
Avanti's role in the five-year project is to supply lipid standards to the investigators so they can standardize their instruments and extracts in order to quantitate the amount of lipid in the macrophage. Shaw told BioWorld Today Avanti has been supplying lipids to the research and pharmaceutical industry since 1969.
Lipids, stored as an energy reserve for the cell, are components of the cell membrane and are involved in communication within and between cells. For example, one class of lipids, the sterols, includes estrogen and testosterone.
Imbalances in lipids might cause or play a role in diseases that affect millions of people, according to the Bethesda, Md.-based NIH. Lipids produced by immune system cells are involved in inflammatory diseases such as rheumatoid arthritis, sepsis, asthma and inflammatory bowel disease. Lipids also are believed to play a role in Alzheimer's disease and cancer.
A detailed understanding of lipid metabolism would be valuable in drug design, UCSD said. Nonsteroidal anti-inflammatory drugs (i.e., aspirin or ibuprofen) belong to a class of drugs that interfere with lipid metabolism. Also, statins, or cholesterol-lowering drugs, alter lipid metabolites, the statement said.
The stated goals of the project are: to separate and detect all lipids in a specific cell and to discover and characterize any novel lipids that might be present, to quantitate each of the lipid metabolites present and to quantitate the changes in their levels and location during cellular function, and to define the biochemical pathways for each lipid and develop lipid maps, which define the interaction networks, Dennis said.
The NIH award was granted through the National Institute of General Medical Sciences (NIGMS). NIGMS believes the project will yield new tools, methods and technologies for sorting out and measuring the changing methods of the 1,000 or more different lipids in a given cell, said Judith Greenberg, NIGMS acting director, in a prepared statement.
The lipid funding is part of the newly coined "glue grant," so named because it allows large-scale biomedical research projects by bringing diverse groups of scientists together.
NIGMS funding to the tune of $6.3 million will support the first year of research.
Other participants include scientists from: Applied Biosystems Group, of Foster City, Calif.; Boston University School of Medicine; Harvard Medical School in Boston; Medical College of Georgia in Augusta; Medical University of South Carolina in Charleston; National Jewish Medical and Research Center in Denver; The Scripps Research Institute in La Jolla, Calif.; University of Michigan Medical School in Ann Arbor; University of Utah in Salt Lake City; and Virginia Commonwealth University in Richmond.